crossing96/oncoscreening huggingface dataset:
Detection of residual tumor cells in bladder biopsy specimens: pitfalls in the interpretation of cytokeratin stains.	Some patients who have had prior bladder biopsies or transurethral resections undergo a repeat resection within several months for various reasons. The detection of a few residual tumor cells in bladder specimens with prior biopsy site changes can be challenging based on histology alone. Immunohistochemistry for cytokeratins may be used as an adjunct in this situation. We have noted several cases in which keratin stains were performed and positive cells were noted, raising the issue as to whether the cytokeratin positive cells were residual tumor cells or stromal cells. Immunohistochemistry for a panel of antibodies [AE1/AE3, CAM 5.2, high molecular weight cytokeratin, smooth muscle actin (SMA), desmin, and anaplastic lymphoma kinase (ALK)] was performed on 29 cases of bladder biopsies with prior biopsy site changes. Of 29 patients, 25 had a prior history of bladder tumor: 17 had invasive high-grade urothelial carcinoma (T1, 5 cases; T2, 11 cases; T3,1 case); 7 had noninvasive high-grade papillary urothelial carcinoma; 1 had noninvasive low-grade papillary urothelial carcinoma). One of the patients with noninvasive high-grade papillary urothelial carcinoma and one of the patents with invasive high-grade urothelial carcinoma had associated carcinoma in-situ. Four patients had prior benign bladder diagnoses: cystitis cystica et glandularis; polypoid cystitis; follicular cystitis; and neurogenic bladder with benign prostate hyperplasia. Of the 29 cases, 6 (21%) had cells with staining for at least 2 of the cytokeratin markers. Cytokeratin (CK) AE1/ AE3 was positive for cells in 8/29 cases (28%). In 6 of these cases, cells displayed a spindle cell and 2 cases a more epithelioid morphology. CAM 5.2 was positive in cells in 5/29 cases (17%); 3 of the cases had spindle cell and 2 cases epithelioid morphology. High molecular weight cytokeratin was expressed in cells in 2/29 cases (7%) with 1 case having spindle cell and 1 epithelioid morphology. SMA was positive in cells with a spindle cell morphology and negative in the more epitheloid cytokeratin positive cells. Desmin was positive in 3/6 keratin positive spindle cells and negative in keratin positive epithelioid cells. ALK was negative in all the cases. Three cases with spindle cell morphology and positivity for at least 1 of the keratins and SMA stains were interpreted as aberrant keratin expression in myofibroblastic cells based on the staining and the morphology of the spindle cells. Another 3 cases with concurrent staining for at least 1 of the keratins, SMA and desmin were consistent with smooth muscle cells on the basis of their cellular morphology. Another 2 cases had cells, which expressed at least 2 CK markers but did not express SMA, desmin, or ALK and a more epithelioid morphology. These cells were interpreted as residual tumors cells. When interpreting CK stains for the detection of residual tumor cells, one should pay attention to the nature of the cells and not assume all CK staining cells are residual tumor cells.	bladder
Human agonistic antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 2 induces cytotoxicity and apoptosis in prostate cancer and bladder cancer cells.	OBJECTIVES: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of tumor cells through two of its receptors: TRAIL-R1 and TRAIL-R2. In this study, we investigated the susceptibility of human prostate cancer and bladder cancer cells to HGS-ETR2, a human monoclonal agonistic antibody specific for TRAIL-R2. METHODS: The cell surface expression of TRAIL-R1 and TRAIL-R2 on prostate cancer and bladder cancer cells was determined using flow cytometry. Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and caspase activities were measured by a quantitative colorimetric assay. RESULTS: HGS-ETR2 effectively induced apoptotic cell death in DU145, PC3, and LNCaP human prostate cancer cells and J82 and T24 human bladder cancer cells. The increased effectiveness of HGS-ETR2 for inducing cell death might have been affected by differences in the cell surface expression of the two TRAIL receptors, in that TRAIL-R2, but not TRAIL-R1, was frequently expressed in the prostate cancer and bladder cancer cells. HGS-ETR2 significantly activated the caspase cascade, including caspase-3, -6, -8, and -9, which were the downstream molecules of the death receptors in prostate cancer cells. Caspase-3, -6, and -9 were also significantly activated with HGS-ETR2-induced apoptosis in the bladder cancer cells. CONCLUSIONS: These findings suggest the potential utility of TRAIL-R2 antibody as a novel therapeutic agent against prostate cancer and bladder cancer.	bladder
PKC inhibitor Go6976 induces mitosis and enhances doxorubicin-paclitaxel cytotoxicity in urinary bladder carcinoma cells.	Protein kinase C (PKC) alpha/betaI isoenzyme inhibitor Go6976 has been suggested to be a G2 checkpoint abrogator by direct Chk1 inhibition. In the present study, we demonstrate that Go6976 induces mitosis in doxorubicin treated G2-arrested 5637 urinary bladder transitional cell carcinoma cells and interestingly also in non-synchronized 5637 cells. Importantly, the results demonstrated that both doxorubicin treated and non-synchronized cancer cells are forced to mitosis by Go6976. However, part of the cells avoid the death in mitosis and continue in the cell cycle which may increase the probability of genomic instability. Cytotoxicity of Go6976 alone and in combination with chemotherapeutic agents was further studied. Go6976 treatment alone induced apoptotic cell death. Cytostatic doxorubicin pre-treatment induced G2 arrest and inhibited the cytotoxic effects of mitosis specific drug paclitaxel. Cytotoxicities of doxorubicin-paclitaxel and doxorubicin-Go6976 sequences could be markedly enhanced by combining Go6976 with paclitaxel after doxorubicin pre-treatment. In doxorubicin-Go6976+paclitaxel sequence, paclitaxel arrested the cells to mitosis and unfavourable progression of the cell cycle was inhibited. Analyzes of the molecular mechanisms underlying Go6976 induced mitosis showed that PKC inhibiting concentrations of Go6976 induced cdc2 activation concentration-dependently in non-synchronized and in DNA damaged cells. Simultaneously, Chk1/2 became deactivated and cdc25C activated in DNA damaged cells, indicating regulatory events upstream. In non-synchronized cells, activation of cdc25C, but not Chk1/2, was observed, suggesting inactivation of c-TAK1. The results of the current study suggest that Go6976 has a synergistic cytotoxic effect when combined with doxorubicin and paclitaxel.	bladder
[Capillary electrophoresis coupled to mass spectrometry for proteome analysis. An innovative diagnostic method for prostate and bladder cancer].	We developed a proteomics-based technology for the non-invasive detection of urothelial and prostate carcinoma. Using capillary electrophoresis coupled to mass spectrometry, disease-specific changes in the urinary proteome were detected and subsequently relevant polypeptides were employed as disease-specific biomarkers. Here we report the results of various studies including approximately 1,000 patients with different diseases and healthy volunteers. The results of these studies revealed that prostate and urothelial carcinoma can be detected by using disease-specific polypeptide patterns. Preliminary results also indicate that the tumour stage of an urothelial carcinoma can be estimated by this approach. In conclusion, this new and non-invasive application might help to improve the diagnostic methods already available.	bladder
[Efficacy of detection of specific nuclear protein of matrix 22 in the urine in diagnosis of urinary bladder cancer].	The method is based on enzyme immunoassay for definition of nuclear matrix proteins forming part of the cell nuclear capsule. Quantity of these proteins increase 20-80 times in cancer of the bladder. A total of 83 patients participated in the trial. Group 1 consisted of 18 patients with primary bladder cancer, group 2 - of 26 patients with histologically confirmed bladder cancer recurrence. Group 3 - 19 patients with operated bladder cancer without recurrent disease for at least 6 months. Control group - 20 healthy donors. The test urine sample was placed into a test hole and 30 min later the result was assessed. Overall sensitivity of the method was 52% (p < 0.05). Sensitivity of the test increases with progression of the disease: T1 - 37%, T2 - 75%, T3 - 80% (p < 0.05); G1 - 30%, G2 - 50%, G3 87% (p < 0.05). Overall specificity was 95% (p < 0.05). Thus, nuclear matrix proteins 22 represent a prospective marker of the bladder cancer with high specificity and sensitivity in defining not only primary tumors but also the disease recurrences.	bladder
Predictive value of p53 and pRb expression in superficial bladder cancer patients treated with BCG and interferon-alpha.	BACKGROUND: Nuclear p53 and retinoblastoma protein (pRb) were reported to be poor prognostic indicators for transitional cell carcinoma of the bladder. The authors sought to determine the prognostic value of nuclear p53 and pRb in superficial bladder transitional cell carcinoma patients who were treated with intravesical bacille Calmette-Guerin (BCG) or BCG with interferon-alpha (IFN-alpha). METHODS: A prospective histological review was performed for 80 superficial bladder transitional cell carcinoma patients who underwent postresection intravesical regimes of BCG (81 mg, n = 33 or 27 mg, n = 20) or BCG (27 mg) with IFN-alpha (n = 27), and followed for a mean of 4.5 years. Hematoxylin and eosin (H & E) and immunoperoxidase staining were performed on tissue sections. Nuclear p53 and pRb immunoreactivity were assessed semiquantitatively, by using a combination of staining extent and intensity, to categorize overexpression or underexpression. Data were analyzed by using chi-square analysis, multiple logistic regression, and Kaplan-Meier curves. RESULTS: pRb expression was not associated with patient outcome after BCG-alone therapy, but pRb underexpression was significantly associated with BCG nonresponse and tumor recurrence (P = .047) after BCG and IFN-alpha (BCG + IFN-alpha) therapy. Low-grade tumors were associated with pRb overexpression, with or without nuclear p53 underexpression (P = .019; P = .043, respectively). p53 expression alone or in combination with pRb expression had no significant relation with tumor response to BCG alone or BCG + IFN-alpha with respect to recurrence, progression, or cancer-specific death. CONCLUSIONS: Nuclear pRb underexpression may be predictive of nonresponse and cancer recurrence after intravesical BCG + IFN-alpha therapy. Nuclear p53 expression or its combination with pRb expression is not associated with post-BCG clinical outcome, so p53 expression or p53 with pRb expression should not be used to influence decisions concerning BCG-alone or BCG + IFN-alpha therapy.	bladder
[Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma: a case report].	We report a case of primary mucosa-associated lympoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma. A 84-year-old woman showed microscopic hematuria during follow up for hypertention. Left renal pelvic tumor was found and she was referred to our hospital for further evaluation and managemant. She showed pyuria and Escherichia coli was detected by urine culture. Intravenous pyelography and computed tomography revealed the left renal pelvic tumor and solid bladder tumor. Transurethral resection of bladder tumor and left total nephroureterectomy were performed. Histologically, the left renal pelvic tumor was urothelial carcinoma > > adenocarcinoma, G2, pT2 and the bladder tumor was MALT lymphoma. Ga-scintigraphy showed no hot uptake suspicious of metastatic lesion. Then, external beam radiotherapy (36 Gy) was performed to the urinary bladder. She has been alive for 14 months with neither renal pelvic tumor nor MALT lymphoma showing any evidence of disease progression.	bladder
HIV-Tat protein transduction domain specifically attenuates growth of polyamine deprived tumor cells.	Polyamines are essential for tumor cell growth, and the polyamine pathway represents an attractive target for cancer treatment. Several polyamine transport proteins have been cloned and characterized in bacteria and yeast cells; however, the mechanism of polyamine entry into mammalian cells remains poorly defined, although a role for proteoglycans has been suggested. Here, we show that the HIV-Tat transduction peptide, which is known to enter cells via a proteoglycan-dependent pathway, efficiently inhibits polyamine uptake. Polyamine uptake-deficient mutant cells with intact proteoglycan biosynthesis (CHO MGBG) displayed unperturbed HIV-Tat uptake activity compared with wild-type cells, supporting the notion that HIV-Tat peptide interferes with polyamine uptake via competition for proteoglycan binding sites rather than a putative downstream transporter. HIV-Tat specifically inhibited growth of human carcinoma cells made dependent on extracellular polyamines by treatment with the polyamine biosynthesis inhibitor alpha-difluoromethylornithine; accordingly, the Tat peptide prevented intracellular accumulation of exogenous polyamines. Moreover, combined treatment with alpha-difluoromethylornithine and HIV-Tat efficiently blocked tumor growth in an experimental mouse model. We conclude that HIV-Tat transduction domain and polyamines enter cells through a common pathway, which can be used to target polyamine-dependent tumor growth in the treatment of cancer.	bladder
Prediction of drug combination chemosensitivity in human bladder cancer.	The choice of therapy for metastatic cancer is largely empirical because of a lack of chemosensitivity prediction for available combination chemotherapeutic regimens. Here, we identify molecular models of bladder carcinoma chemosensitivity based on gene expression for three widely used chemotherapeutic agents: cisplatin, paclitaxel, and gemcitabine. We measured the growth inhibition elicited by these three agents in a series of 40 human urothelial cancer cell lines and correlated the GI(50) (50% of growth inhibition) values with quantitative measures of global gene expression to derive models of chemosensitivity using a misclassification-penalized posterior approach. The misclassification-penalized posterior-derived models predicted the growth response of human bladder cancer cell lines to each of the three agents with sensitivities of between 0.93 and 0.96. We then developed an in silico approach to predict the cellular growth responses for each of these agents in the clinically relevant two-agent combinations. These predictions were prospectively evaluated on a series of 15 randomly chosen bladder carcinoma cell lines. Overall, 80% of the predicted combinations were correct (P = 0.0002). Together, our results suggest that chemosensitivity to drug combinations can be predicted based on molecular models and provide the framework for evaluation of such models in patients undergoing combination chemotherapy for cancer. If validated in vivo, such predictive models have the potential to guide therapeutic choice at the level of an individual's tumor.	bladder
Pseudosarcomatous and sarcomatous proliferations of the bladder.	Pseudosarcomatous fibromyxoid tumor (PFT), postoperative spindle cell nodule (PSN), sarcoma, and sarcomatoid carcinoma of the bladder are frequently difficult to distinguish histopathologically with significant differences in disease-related outcomes. A retrospective review of our pathology registry over the last 25 years identified 7 PFT, 10 PSN, 18 primary bladder sarcomas, and 17 sarcomatoid carcinomas. Most patients with PFT, PSN, sarcoma, and sarcomatoid carcinoma were diagnosed between the ages of 50 to 60 years with PFT and PSN most commonly detected in women. A previous history of urological instrumentation and bladder cancer was present in all patients with PSN but none of the patients with PFT. Pseudosarcomatous fibromyxoid tumors were characterized by a tissue culture-like proliferation of myofibroblastic cells with focal atypia and overall cytoarchitectural features mimicking nodular fasciitis. Sarcomas and sarcomatoid carcinomas exhibited cellular atypia, mitotic activity with atypical mitosis, and the presence of necrosis. Transurethral resection was sufficient to control all PFT and PSN with no evidence of distant metastatic spread. In contrast, local recurrences and distant metastases frequently occurred in patients with primary sarcoma and sarcomatoid carcinoma despite aggressive surgical management, which was often combined with neoadjuvant chemotherapy (50% and 65% disease-specific mortality, respectively). Pseudosarcomatous fibromyxoid tumor and PSN have unique clinical and pathologic features that allow their distinction from primary bladder sarcoma and sarcomatoid carcinoma.	bladder
Bladder cancer incidence and risk factors in men with prostate cancer: results from Cancer of the Prostate Strategic Urologic Research Endeavor.	PURPOSE: We evaluated a large disease registry to determine the incidence of bladder cancer in patients with prostate cancer and investigate whether the type of treatment for prostate cancer increased the risk of bladder cancer. MATERIALS AND METHODS: We analyzed the CaPSURE disease registry for men diagnosed with prostate cancer plus bladder cancer between 1989 and 2003. Demographics, comorbidities and prostate cancer treatment modalities were compared in patients with and without bladder cancer. A backward stepwise Cox proportional hazards regression model was used to predict bladder cancer onset after treatment for prostate cancer in patients who had bladder cancer 30 days or greater after prostate cancer treatment. RESULTS: Of 9,780 patients from CaPSURE 143 (1.46%) also had bladder cancer. Patients with bladder cancer and prostate cancer were older (p<0.01) and more likely to be white (p=0.03), and they had lower levels of income (p<0.01) and education (p=0.04) than patients with prostate cancer only. Comorbidities did not differ between patients with and without bladder cancer. Patients treated with radical prostatectomy were approximately half as likely to have posttreatment bladder cancer as patients who underwent radiation therapy (HR 0.51, 95% CI 0.29-0.89). Patients who smoked had an independent increase in the risk of bladder cancer (HR 2.08, 95% CI 1.09-3.97), while smokers treated with radiation therapy were at almost 4-fold risk for bladder cancer (HR 3.65, 95% CI 1.45-9.16). CONCLUSIONS: The incidence of bladder cancer in patients with prostate cancer was 1.5%. Radiation therapy and smoking increased the risk of bladder cancer.	bladder
Pattern of recurrence changes in noninvasive bladder tumors observed during 2 decades.	PURPOSE: Previously published data on the 25-year outcome of G1Ta and G2Ta bladder tumors demonstrated that both tumors have a similarly low risk of recurrence in cases in which no tumor was detected in the first 5 years after presentation. A further 4 prospectively maintained cohorts were available for comparison between institutions or across time periods. MATERIALS AND METHODS: Review of a prospectively kept, computerized record of patients with bladder cancer allowed analysis of the long-term outcome of 4 further cohorts of bladder cancer presenting in 1978 to 1986 or 1991 to 1996. RESULTS: A total of 325 patients with G1Ta and 190 with G2Ta bladder tumors had up to 25 years of followup. The risk of recurrence in the first 5 years was identical in all cohorts from the 1980s. However, in those patients without recurrence in the initial 5 years, the subsequent risk of recurrence (in G1 and G2Ta tumors) was 3.2% in the earlier cohorts but increased 3-fold to 10.8% in the cohorts from the early 1990s (RR 3.3, 95% CI 1.2-9.5, p=0.016). CONCLUSIONS: A difference was observed in the pattern of late biopsy proven recurrence in the more contemporary cases. Increased use of prophylactic intravesical chemotherapy does not seem to be a strong factor. Changes in the ability to detect lesions and the readiness to biopsy suspicious lesions may be responsible for this difference.	bladder
Protein networking in bladder cancer: immunoreactivity for FGFR3, EGFR, ERBB2, KAI1, PTEN, and RAS in normal and malignant urothelium.	A panel of markers, selected for the suspected bladder cancer relevance of their corresponding genes, were explored for their expression and subcellular location in urinary bladder tissue. The expression in normal urothelium, in non-metastasised transitional cell carcinomas (TCC), and in primary metastasised TCC with corresponding metastases was mapped. Potential associations between the proteins were identified. The observations were then combined in a set of hypotheses aimed at further hypothesis testing. Membranous ERBB4 and cytoplasmic p21RAS were downregulated in carcinoma cells compared with normal urothelium cells. FGFR3 was translocated from the cytoplasm to the nucleus. ERBB2 was translocated to the membrane and seemingly upregulated in one subgroup and conversely downregulated in another. EGFR, KAI1 and possibly PTEN revealed increased membranous immunoreactivity in non-metastasised tumours. The metastases showed decreased nuclear FGFR3 and membranous PTEN staining compared with corresponding primary tumours. EGFR expression was positively correlated with the expression of PTEN and FGFR3. The expression of ERBB2 was negatively correlated with p21RAS expression. According to our results, bladder carcinogenesis comprises FGFR3 translocation to the nucleus, upregulation of EGFR, ERBB2, KAI1 and PTEN; downregulation of p21RAS; and translocation of EGFR, ERBB2, and possibly PTEN to the membrane. Our results support the hypotheses regarding PTEN and KAI1 functioning as tumour suppressors in bladder cancer. EGFR and KAI1 may discriminate between non-metastasised and metastasised cancers. A complex network of associations between the factors is suggested.	bladder
Overexpression of CD24: association with invasiveness in urothelial carcinoma of the bladder.	CONTEXT: CD24, originally described as a B-cell marker, has gained considerable attention in tumor research. High rates of CD24 expression have been found in several types of carcinomas that are significantly associated with a more aggressive course of the disease. To our knowledge, the expression of CD24 in urothelial carcinoma (UC) of the bladder has not been previously reported. OBJECTIVE: To determine the expression of CD24 in UCs and the association between CD24 levels and tumor grade and stage. DESIGN: Urothelial carcinomas (48 cystectomy, 87 transurethral biopsy), including 56 pTa, 29 pT1, 19 pT2, and 31 pT3, were analyzed immunohistochemically using an anti-CD24 monoclonal antibody. The intensity of CD24 staining was semiquantitatively scored as high-level or low-level expression. RESULTS: In normal urothelium, CD24 was localized to the cytoplasm of the luminal cell layer with very low intensity. CD24 expression was upregulated in noninvasive UCs, and a high level of expression was correlated with the tumor grade (P = .003). Invasive UCs demonstrated strong diffuse cytoplasmic overexpression of CD24 and the difference in CD24 expression between invasive and noninvasive UC was statistically significant (P < .001). CONCLUSIONS: CD24 protein is overexpressed in a significant number of bladder UCs. The high level of CD24 expression with loss of apical localization is a marker for stromal invasion and high tumor grade in UC. This study provides the basis for future investigations of CD24 as a potential serum marker or target of antibody-based therapeutics in bladder UC.	bladder